FDA approves Fasenra for treating adults with rare AAV form EGPA
Trial results showed therapy led to remission in nearly 60% of patients
The U.S. Food and Drug Administration (FDA) has approved Fasenra (benralizumab) for treating adults with eosinophilic granulomatosis with polyangiitis (EGPA), a rare form of ANCA-associated vasculitis (AAV).
Developed by AstraZeneca, Fasenra was already approved in more than 80 countries, including the U.S., as an add-on treatment for severe eosinophilic asthma, a form of asthma marked by high numbers of immune cells called eosinophils.
The expanded approval for EGPA is based largely on results from the Phase 3 MANDARA clinical trial (NCT04157348), which showed that Fasenra was at least as effective as Nucala (mepolizumab) — the only previously approved EGPA therapy — in treating patients. In that trial, the newly approved therapy led to remission in nearly 60% of participants, with 41% being able to stop standard treatment with oral glucocorticoids.
Glucocorticoids are a class of corticosteroid hormones, typically just called steroids, that have anti-inflammatory and immunosuppressive effects; they are commonly used as a treatment for EGPA.
“Patients often rely on long-term oral corticosteroids, which can cause serious and lasting side effects,” Michael Wechsler, MD, a professor of medicine at National Jewish Health and an investigator in the MANDARA trial, said in a press release from AstraZeneca.
“[Fasenra] is a much-needed treatment option, with data showing that not only is remission an achievable goal for EGPA patients, but [Fasenra] can also help patients taper off steroid therapy,” Wechsler said.
Therapy helped 41% of trial participants stop steroids
In EGPA patients, Fasenra will be administered at a dose of 30 mg via a monthly subcutaneous, or under-the-skin, injection. It is available as a single-dose prefilled syringe, given by a healthcare provider, and as a single-dose autoinjector pen that can be administered, with proper training, by patients themselves or by caregivers.
The list price for a 30 mg dose is $5,511.41, but out-of-pocket costs will depend on each patient’s insurance type. According to AstraZeneca, the average out-of-pocket cost for people with employer or individual private insurance is $46 per dose.
“With this approval, physicians in the US will now be able to offer an important new, convenient single monthly subcutaneous injection to their patients with EGPA,” said Ruud Dobber, PhD, executive vice president of the biopharmaceuticals business unit at AstraZeneca. “[This] news demonstrates the potential of Fasenra to help patients suffering from eosinophilic diseases beyond severe asthma.”
All types of AAV are marked by inflammation and damage to small blood vessels, with EGPA being further characterized by high levels of eosinophils. These immune cells defend the body against harmful invaders, but are also linked to allergy and asthma-associated inflammation.
With this approval, physicians in the US will now be able to offer an important new, convenient single monthly subcutaneous injection to their patients with EGPA. … [This] news demonstrates the potential of Fasenra to help patients suffering from eosinophilic diseases beyond severe asthma.
EGPA results in damage to multiple organs throughout the body. About half of EGPA patients have adult-onset severe eosinophilic asthma with sinus and nasal symptoms, according to AstraZeneca. The sinuses are cavities within the face that are typically filled with air.
While the disease is commonly treated with glucocorticoids, their long-term use is associated with a range of serious side effects.
Fasenra is an antibody-based treatment designed to prevent the activation of IL-5 receptor alpha (IL-5R-alpha), a protein found almost exclusively on the surface of eosinophils and whose activation is critical for the cells’ growth and survival.
In doing so, and by also promoting the binding of other immune cells to Fasenra-covered eosinophils, the therapy boosts eosinophil death both indirectly and directly and helps limit eosinophil-mediated inflammation. This is expected to help drive EGPA disease remission while reducing the need for glucocorticoids.
Fasenra tested against Nucala in EGPA clinical trial
The therapy’s mechanism of action is similar, but somewhat different, to that of GSK’s Nucala, an antibody-based treatment that indirectly promotes eosinophil death by targeting IL-5, the protein in circulation that activates IL-5R-alpha.
MANDARA was a head-to-head trial designed to compare the safety and efficacy of Fasenra against Nucala in 140 adults with difficult-to-treat EGPA. The participants had experienced recent disease relapses, failed to achieve remission with standard therapy, or had symptom recurrence when glucocorticoids were tapered off.
Each patient was randomly assigned to receive either a single 30 mg subcutaneous injection of Fasenra or three separate 100 mg subcutaneous injections of Nucala every four weeks on top of standard care for about a year.
The results showed that remission rates were similar between the two groups, with 59% of those on Fasenra and 57% on Nucala achieving disease remission. Moreover, in the last month of treatment, a higher proportion of Fasenra-treated patients were able to fully taper off oral glucocorticoids compared with the Nucala group (41% vs. 26%).
Per the prescribing label, the most common side effects of Fasenra include headache and sore throat.
“This disease has a devastating impact on patients and the quality of their life, and they need more treatment options,” said Joyce Kullman, executive director of the Vasculitis Foundation. “The approval of another treatment in EGPA is welcome news to the approximately 15,000 patients living in the US with this difficult-to-treat rare disease.”
Fasenra is also being developed for other diseases in which eosinophils are implicated, including chronic obstructive pulmonary disease.
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